The epothilones (1-5) are natural substances which exhibit cytotoxicity even against paclitaxel-resistant tumor cells by promoting the polymerization of α- and β-tubulin subunits and stabilizing the resulting microtubule assemblies. Epothilones displace paclitaxel (the active principle of TAXOL™) from its microtubuli binding site and are reported to be more potent than paclitaxel with respect to the stabilization of microtubules.

What is needed are analogs of epothilone A and B that exhibit superior pharmacological properties, especially one or more of the following properties: an enhanced therapeutic index (e.g. a larger range of cytotoxic doses against e.g. proliferative diseases without toxicity to normal cells), better pharmakokinetic properties, better pharmacodynamic properties, better solubility in water, better efficiency against tumor types that are or become resistant to treatment with one or more other chemotherapeutics, better properties to facilitate manufacture of formulations, e.g. better solubility in polar solvents, especially those comprising water, enhanced stability, convenient manufacture of the compounds as such, improved inhibition of proliferation at the cellular level, high levels of microtubule stabilizing effects, and/or specific pharmacologic profiles.